The overall objective of this research renewal proposal is to further study the basic similarities and differences between methadone, LAAM and morphine in rats prepared with chronic electrodes for recording of the EEG and EMG activities, in addition to silicon rubber cannulas implanted into the jugular vein for administering the narcotics. The changes in EEG and sleep-awake cycle will be assessed during the process of development of tolerance and physical dependence, the "drug-seeking" behavior through bar-pressing and self-injection, the time-course and severity of abstinence and the persistence of long-term EEG and behavioral effects. The relative low margin of safety for methadone in methadone dependent rats will be further assessed in a dose response relationship. In LAAM dependent rats, the ratio of convulsant dose to the dose which blocks bar-pressing behavior will also be delineated. Naloxone induced abstinence will be produced in rats self-maintaining their dependence on morphine, methadone and LAAM. The effects of this treatment on the voltage output and frequency spectra of the EEG and behavior will then be evaluated and compared to assess the degree of physical dependence established during self-administration of these narcotics and their withdrawal effects on the EEG and behavior. Structure-activity relationships of the currently available narcotic antagonists and their different preparations and metabolites will be studied. The relation between the chemical structure and the suppression of drug-seeking behavior will be assessed as to potency, duration of action and effective routes of administration. The effects of the narcotic antagonists and different naltrexone preparations on the "drug- seeking" behavior of post-addict rats and, the phenomenon of relapse, will also be determined by evaluation of the rate of lever-pressing activity for morphine self-injection leading to extinction or to the re-establishment of dependence in rats chronically treated with the antagonists and given access to morphine.